Dietary influences on tissue concentrations of phytanic acid and AMACR expression in the benign human prostate

Yachana Kataria, Margaret Wright, Ryan J. Deaton, Erika Enk Rueter, Benjamin A. Rybicki, Ann B. Moser, Vijayalakshmi Ananthanrayanan, Peter H. Gann

Research output: Contribution to journalArticle

Abstract

BACKGROUND. Alpha-methylacyl-CoA racemase (AMACR) is an enzyme involved in fatty acid metabolism that is markedly over-expressed in virtually all prostate cancers (PCa), relative to benign tissue. One of AMACR's primary substrates, phytanic acid, is derived predominately from red meat and dairy product consumption. Epidemiological evidence suggests links between dairy/red meat intake, as well as phytanic acid levels, and elevated PCa risk. This study investigates the relationships among dietary intake, serum and tissue concentrations of phytanic acid, and AMACR expression (mRNA and protein) in the histologically benign human prostate. METHODS. Men undergoing radical prostatectomy for the treatment of localized disease provided a food frequency questionnaire (n = 68), fasting blood (n = 35), benign fresh frozen prostate tissue (n = 26), and formalin-fixed paraffin-embedded (FFPE) sections (n = 67). Serum and tissue phytanic acid concentrations were obtained by gas chromatography-mass spectrometry. We extracted RNA from epithelial cells using laser capture microdissection and quantified mRNA expression of AMACR and other genes involved in the peroxisomal phytanic acid metabolism pathway via qRT-PCR. Immunohistochemistry for AMACR was performed on FFPE sections and subsequently quantified via digital image analysis. Associations between diet, serum, and tissue phytanic acid levels, as well as AMACR and other gene expression levels were assessed by partial Spearman correlation coefficients. RESULTS. High-fat dairy intake was the strongest predictor of circulating phytanic acid concentrations (r = 0.35, P = 0.04). Tissue phytanic acid concentrations were not associated with any dietary sources and were only weakly correlated with serum levels (r =0.29, P = 0.15). AMACR gene expression was not associated with serum phytanic acid (r = 0.13, P = 0.47), prostatic phytanic acid concentrations (r = 0.03, P = 0.88), or AMACR protein expression (r = 0.16, P = 0.20). CONCLUSIONS. Our data underscore the complexity of the relationship between AMACR and its substrates and do not support the unifying hypothesis that excess levels of dietary phytanic acid are responsible for both the overexpression of AMACR in prostate cancer and the potential association between PCa risk and intake of dairy foods and red meat.

Original languageEnglish (US)
Pages (from-to)200-210
Number of pages11
JournalProstate
Volume75
Issue number2
DOIs
StatePublished - Feb 1 2015

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Phytanic Acid
Prostate
Prostatic Neoplasms
Serum
Paraffin
Formaldehyde
alpha-methylacyl-CoA racemase
Laser Capture Microdissection
Gene Expression
Messenger RNA
Meat Products
Dairy Products
Prostatectomy
Gas Chromatography-Mass Spectrometry

Keywords

  • AMACR
  • Biomarker
  • Diet
  • Phytanic acid
  • Prostate cancer

ASJC Scopus subject areas

  • Urology
  • Oncology
  • Medicine(all)

Cite this

Kataria, Y., Wright, M., Deaton, R. J., Rueter, E. E., Rybicki, B. A., Moser, A. B., ... Gann, P. H. (2015). Dietary influences on tissue concentrations of phytanic acid and AMACR expression in the benign human prostate. Prostate, 75(2), 200-210. https://doi.org/10.1002/pros.22905

Dietary influences on tissue concentrations of phytanic acid and AMACR expression in the benign human prostate. / Kataria, Yachana; Wright, Margaret; Deaton, Ryan J.; Rueter, Erika Enk; Rybicki, Benjamin A.; Moser, Ann B.; Ananthanrayanan, Vijayalakshmi; Gann, Peter H.

In: Prostate, Vol. 75, No. 2, 01.02.2015, p. 200-210.

Research output: Contribution to journalArticle

Kataria, Y, Wright, M, Deaton, RJ, Rueter, EE, Rybicki, BA, Moser, AB, Ananthanrayanan, V & Gann, PH 2015, 'Dietary influences on tissue concentrations of phytanic acid and AMACR expression in the benign human prostate', Prostate, vol. 75, no. 2, pp. 200-210. https://doi.org/10.1002/pros.22905
Kataria, Yachana ; Wright, Margaret ; Deaton, Ryan J. ; Rueter, Erika Enk ; Rybicki, Benjamin A. ; Moser, Ann B. ; Ananthanrayanan, Vijayalakshmi ; Gann, Peter H. / Dietary influences on tissue concentrations of phytanic acid and AMACR expression in the benign human prostate. In: Prostate. 2015 ; Vol. 75, No. 2. pp. 200-210.
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abstract = "BACKGROUND. Alpha-methylacyl-CoA racemase (AMACR) is an enzyme involved in fatty acid metabolism that is markedly over-expressed in virtually all prostate cancers (PCa), relative to benign tissue. One of AMACR's primary substrates, phytanic acid, is derived predominately from red meat and dairy product consumption. Epidemiological evidence suggests links between dairy/red meat intake, as well as phytanic acid levels, and elevated PCa risk. This study investigates the relationships among dietary intake, serum and tissue concentrations of phytanic acid, and AMACR expression (mRNA and protein) in the histologically benign human prostate. METHODS. Men undergoing radical prostatectomy for the treatment of localized disease provided a food frequency questionnaire (n = 68), fasting blood (n = 35), benign fresh frozen prostate tissue (n = 26), and formalin-fixed paraffin-embedded (FFPE) sections (n = 67). Serum and tissue phytanic acid concentrations were obtained by gas chromatography-mass spectrometry. We extracted RNA from epithelial cells using laser capture microdissection and quantified mRNA expression of AMACR and other genes involved in the peroxisomal phytanic acid metabolism pathway via qRT-PCR. Immunohistochemistry for AMACR was performed on FFPE sections and subsequently quantified via digital image analysis. Associations between diet, serum, and tissue phytanic acid levels, as well as AMACR and other gene expression levels were assessed by partial Spearman correlation coefficients. RESULTS. High-fat dairy intake was the strongest predictor of circulating phytanic acid concentrations (r = 0.35, P = 0.04). Tissue phytanic acid concentrations were not associated with any dietary sources and were only weakly correlated with serum levels (r =0.29, P = 0.15). AMACR gene expression was not associated with serum phytanic acid (r = 0.13, P = 0.47), prostatic phytanic acid concentrations (r = 0.03, P = 0.88), or AMACR protein expression (r = 0.16, P = 0.20). CONCLUSIONS. Our data underscore the complexity of the relationship between AMACR and its substrates and do not support the unifying hypothesis that excess levels of dietary phytanic acid are responsible for both the overexpression of AMACR in prostate cancer and the potential association between PCa risk and intake of dairy foods and red meat.",
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AU - Kataria, Yachana

AU - Wright, Margaret

AU - Deaton, Ryan J.

AU - Rueter, Erika Enk

AU - Rybicki, Benjamin A.

AU - Moser, Ann B.

AU - Ananthanrayanan, Vijayalakshmi

AU - Gann, Peter H.

PY - 2015/2/1

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N2 - BACKGROUND. Alpha-methylacyl-CoA racemase (AMACR) is an enzyme involved in fatty acid metabolism that is markedly over-expressed in virtually all prostate cancers (PCa), relative to benign tissue. One of AMACR's primary substrates, phytanic acid, is derived predominately from red meat and dairy product consumption. Epidemiological evidence suggests links between dairy/red meat intake, as well as phytanic acid levels, and elevated PCa risk. This study investigates the relationships among dietary intake, serum and tissue concentrations of phytanic acid, and AMACR expression (mRNA and protein) in the histologically benign human prostate. METHODS. Men undergoing radical prostatectomy for the treatment of localized disease provided a food frequency questionnaire (n = 68), fasting blood (n = 35), benign fresh frozen prostate tissue (n = 26), and formalin-fixed paraffin-embedded (FFPE) sections (n = 67). Serum and tissue phytanic acid concentrations were obtained by gas chromatography-mass spectrometry. We extracted RNA from epithelial cells using laser capture microdissection and quantified mRNA expression of AMACR and other genes involved in the peroxisomal phytanic acid metabolism pathway via qRT-PCR. Immunohistochemistry for AMACR was performed on FFPE sections and subsequently quantified via digital image analysis. Associations between diet, serum, and tissue phytanic acid levels, as well as AMACR and other gene expression levels were assessed by partial Spearman correlation coefficients. RESULTS. High-fat dairy intake was the strongest predictor of circulating phytanic acid concentrations (r = 0.35, P = 0.04). Tissue phytanic acid concentrations were not associated with any dietary sources and were only weakly correlated with serum levels (r =0.29, P = 0.15). AMACR gene expression was not associated with serum phytanic acid (r = 0.13, P = 0.47), prostatic phytanic acid concentrations (r = 0.03, P = 0.88), or AMACR protein expression (r = 0.16, P = 0.20). CONCLUSIONS. Our data underscore the complexity of the relationship between AMACR and its substrates and do not support the unifying hypothesis that excess levels of dietary phytanic acid are responsible for both the overexpression of AMACR in prostate cancer and the potential association between PCa risk and intake of dairy foods and red meat.

AB - BACKGROUND. Alpha-methylacyl-CoA racemase (AMACR) is an enzyme involved in fatty acid metabolism that is markedly over-expressed in virtually all prostate cancers (PCa), relative to benign tissue. One of AMACR's primary substrates, phytanic acid, is derived predominately from red meat and dairy product consumption. Epidemiological evidence suggests links between dairy/red meat intake, as well as phytanic acid levels, and elevated PCa risk. This study investigates the relationships among dietary intake, serum and tissue concentrations of phytanic acid, and AMACR expression (mRNA and protein) in the histologically benign human prostate. METHODS. Men undergoing radical prostatectomy for the treatment of localized disease provided a food frequency questionnaire (n = 68), fasting blood (n = 35), benign fresh frozen prostate tissue (n = 26), and formalin-fixed paraffin-embedded (FFPE) sections (n = 67). Serum and tissue phytanic acid concentrations were obtained by gas chromatography-mass spectrometry. We extracted RNA from epithelial cells using laser capture microdissection and quantified mRNA expression of AMACR and other genes involved in the peroxisomal phytanic acid metabolism pathway via qRT-PCR. Immunohistochemistry for AMACR was performed on FFPE sections and subsequently quantified via digital image analysis. Associations between diet, serum, and tissue phytanic acid levels, as well as AMACR and other gene expression levels were assessed by partial Spearman correlation coefficients. RESULTS. High-fat dairy intake was the strongest predictor of circulating phytanic acid concentrations (r = 0.35, P = 0.04). Tissue phytanic acid concentrations were not associated with any dietary sources and were only weakly correlated with serum levels (r =0.29, P = 0.15). AMACR gene expression was not associated with serum phytanic acid (r = 0.13, P = 0.47), prostatic phytanic acid concentrations (r = 0.03, P = 0.88), or AMACR protein expression (r = 0.16, P = 0.20). CONCLUSIONS. Our data underscore the complexity of the relationship between AMACR and its substrates and do not support the unifying hypothesis that excess levels of dietary phytanic acid are responsible for both the overexpression of AMACR in prostate cancer and the potential association between PCa risk and intake of dairy foods and red meat.

KW - AMACR

KW - Biomarker

KW - Diet

KW - Phytanic acid

KW - Prostate cancer

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